Relapsed and refractory hematologic acute myeloid leukemia (AML) has a poor response to standard therapy and is associated with a poor prognosis. For example, relapsed AML is a highly aggressive and resistant disease, particularly when associated with a first complete response (CR) duration of less than 12 months. Rates of second remission after such a rapid relapse are lower (25-30% vs. 60%), and remissions are briefer. A recent study from the leukemia group at Princess Margaret Hospital demonstrated that the overall response to reinduction chemotherapy was approximately 50%, but the patients relapsed shortly thereafter if not transplanted. Patients over age 60, with poor risk cytogenetics and/or over 80% blasts in the marrow at reinduction had particularly poor responses to reinduction with a CR rate of approximately 20%. Older patients in particular tend to do poorly with reinduction due to a combination of co-morbid conditions and cumulative hematologic and nonhematologic toxicity. Allogeneic bone marrow transplantation is the only curative option for patients obtaining a second remission, but this treatment modality is not universally available due to lack of related or unrelated donors, patient's age, or the patient's co-morbidities.
Several studies have shown that elevated levels of LDH are a strong prognostic factor in patients with AML, correlating with poor prognosis and response to therapy as well as to an increased likelihood of tumor lysis syndrome.
Thus, there is an urgent need for new agents in relapsed and refractory hematologic malignancies such as acute leukemia. In elderly patients, where the tolerance of aggressive induction therapy is often poor and curative options such as bone marrow transplantation are not available, the need for effective non-aggressive drug regimens for AML is even greater.